Technical Field
The present invention relates to a device for extracting or filtering a fluid, said fluid optionally containing one or more target molecules, such as, but not limited to, common components of interstitial fluid, blood and/or gastrointestinal fluid. The present invention further relates to materials which may form part of such a device and methods employing such a device and such materials. The device, associated materials and methods may find application in the medical field, particularly, but not exclusively in the treatment of uraemia and/or kidney/renal failure.
Background of the Invention
Native kidneys generate a flow of fluid from the systemic vasculature to the urinary system ending in the bladder prior to voiding. The common and highly generalised view of this function of fluid loss is to rid the body of toxic metabolic waste because in the absence of any renal function death from uraemia ensues within days, uremia being defined as a medical condition in which kidney function regresses and the kidney fails to excrete into urine the substances that it would otherwise normally have removed. As a result of suffering this loss of kidney function uremic retention products, i.e. substances which are insufficiently removed as a result of the failing kidneys, accumulate. Uremic toxins are classified as those uremic retention products which have been shown to exert, typically deleterious, biological or biochemical activity which would not occur if the kidneys were functioning normally.
Another process, which is equally important, is control of body fluid volume and ion balance (Na+; Ca2+, K+, Cl−, PO4− etc). About 42% of the total body water is extracellular with large variation in the organ distribution of this water—varying from about 13% of total tissue water for skeletal muscle, up to 70% for skin and connective tissue. During conventional dialysis (peritoneal or haemodialysis), excess fluid is removed from the systemic vascular circulation of uraemic patients. The excess fluid is, however, mainly located in the skin and subcutaneous interstitial tissues.
The interstitium is a metabolically active compartment (lactate concentration is higher than plasma), it surrounds cells, maintaining homeostasis and in uraemic individuals, provides a reservoir for extracellular toxins. Unlike the circulatory system, the interstitial albumin concentration is significantly lower than in serum demonstrated both in adipose tissue (15% of serum) and skeletal muscle (27% of serum). A dynamic equilibrium exists between the extracellular interstitial pool and the vascular compartment as demonstrated by conventional dialysis.
Loss of kidney function resulting in end-stage renal failure is a major clinical problem with a wide variety of causes. In the UK, over 37,000 people are receiving renal replacement therapy (RRT) at a cost of £1.5 billion per annum (2% of the total NHS budget). With over 5,000 new additions per year, the UK Renal Registry predicts that the number of patients will rise to 60,000 by 2020. Similar increases in incident patients are expected in the developed heathcare systems in USA and Europe. In the developing world, RRT is highly restricted or absent due to cost and lack of trained healthcare personnel such that renal failure is essentially a death sentence for most (as it was pre-1970 in UK). With the developing economies of China and India able to support improved healthcare for their populations, there is potential to treat renal failure in an additional 2-3 billion population providing the therapy can be delivered in a less technological environment and at cheaper cost than currently available.
The current options for renal replacement therapy (RRT) are predominantly only available in healthcare systems of the developed world.
A first option is kidney transplantation. Although transplantation provides a better treatment and quality of life, with a one year survival rate of 97% compared 84% on dialysis, in the UK only 1,500 kidneys are available annually, with a transplant waiting list of over 5,000 and growing. Those likely to receive a transplant are younger (median age 49 years, with less cardiovascular and other comorbidities) than those on dialysis (peritoneal 58, haemodialysis 64 years), which leaves an expanding population of older patients for whom transplantation is not a realistic option.
Current dialysis provision is either haemodialysis or peritoneal dialysis. Haemodialysis involves connecting the patient's blood circulation via a surgically constructed arterio-venous fistula or graft to an external machine that allows removal of low molecular weight metabolites and water across a semi permeable membrane with return of the “cleansed” blood to the patient. This is predominantly provided in hospital requiring the patient to attend a minimum of 3 days per week (at least 3×4 hour sessions). Significant clinical problems with this modality include failure of vascular access and sepsis and the patient must meet a level of cardiovascular fitness. Quality of life is poor if the patient has to spend 3 days a week in hospital. There is growing evidence of improved patient outcome with frequent or continuous dialysis but this has logistical constraints and not feasible with current dialysis technology.
Peritoneal dialysis uses the patient's own peritoneal membrane (lining the peritoneal cavity and the visceral organs) as a semi-permeable membrane. With a permanent peritoneal catheter in place, 2 litres of an osmotic solution are in-fused into the peritoneum and after a 4 hour dwell period, the solution is drained out. Low molecular weight metabolites and water from the myriad blood capillaries in the membrane are driven by the osmotic gradient into the in dwelling dialysis solution. This sequence is repeated 3 or 4 times in 24 hour period. Automated versions of this modality allow the patient to connect overnight to a machine that provides frequent flushing of the peritoneal cavity.
Significant clinical problems with this modality include failure of the ultrafiltration function of the membrane and excessive membrane scarring which lead to technique failure.
An object of the present invention is to obviate or mitigate one or more of the aforementioned problems.